Sex differences in normative modeling of cortical thickness in cannabis use disorder

Cannabis use disorder (CUD) is associated with sexually dimorphic behavioral and neurobiological effects, but sex differences in a broader sampling of brain structures in CUD assessed relative to normative reference values have not been examined. Here, we assessed sex differences in brain regions measured via 3 T MRI in 72 adults (50 males, 22 females) with CUD. T1-weighted images, segmented via FreeSurfer, were used to derive Normative Morphometry Imaging Statistics z-scores (accounting for age, sex, intracranial volume, and image quality). Z-scores were then compared between sexes and associated with behavioral data. We found that average z-scores were within normative ranges for both sexes. There were no sex differences in total brain, cerebral white matter, and subcortical gray matter z-scores, but total cortical thickness z-scores were greater in females. Fourteen cortical regions surrounding the central and lateral sulci had greater z-scores in females than in males, but the medial orbitofrontal cortex z-score was greater in males. Of these regions, 3 were positively correlated with cannabis-related problems. Findings suggest sexual dimorphism in brain structure in CUD primarily in the frontal, medial parietal, and superior temporal lobes, with some association with cannabis-related problems even in the context of normative brain structure. Future research is needed to clarify causal mechanisms of morphometric differences in CUD.